Interrogating Biological Signaling Pathway Dysregulations and In Vitro Screening With Personalized Therapies in Relapsed or Refractory Mantle Cell Lymphoma, MCL MATCH Trial

PRIMARY OBJECTIVE:

I. To evaluate the feasibility of the proposed therapy based on dysregulated cell signaling pathways in combination with in vitro drug activity.

SECONDARY OBJECTIVES:

I. Overall response rates (complete response [CR] + partial response [PR]). II. Safety in patients who were treated with matched personalized therapies. III. Duration of response. IV. Progression free survival (PFS). V. Overall survival (OS).

EXPLORATORY OBJECTIVE:

I. Correlation of somatic mutations in MCL with cell signaling dysregulated activity and therapeutic implications of somatic mutations in relapsed MCL.

OUTLINE:

Patients undergo blood, saliva or tissue sample collection for messenger ribonucleic acid analysis (mRNA) analysis and drug efficacy testing. Patients assigned treatment per the results are followed every 1 cycle of therapy for 1 year, every 2 months for 1 year, every 4 months for 1 year then every 6 months thereafter.

Inclusion criteria

• Confirmed MCL tissue diagnosis with CD20- and Cyclin D1-positive cells or cyclin D1 negative but t (11;14) positive and diagnosis confirmed by pathologist from the tissue biopsy.
• Patients must have relapsed/refractory MCL.
• Understand and voluntarily sign an IRB-approved informed consent form.
• Patients must have a biopsy-accessible lesion and be willing to undergo biopsy.
• Patients must have bi-dimensional measurable disease per Cheson criteria (bone marrow or GI-only involvement is acceptable).
• Age ≥ 18 years at the time of signing the informed consent.
• Absolute neutrophil count ≥ 1.0 x 109/L, absolute lymphocyte count ≥ 0.6 x 109/L, platelet count ≥ 50 x 109/L
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Patients must have adequate organ function for drugs(s) or combination being utilized (dependent on the drug (s) being given, the acceptable values of clinical parameters are given below: Biochemical values should be within the following limits:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
• Creatinine clearance (CLcr) > 30 mL/min
• Cardiac ejection fraction ≥ 50% by ECHO or MUGA.
• Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test. Men must agree not to father a child and agree to use a condom if his partner is of child-bearing potential.

Exclusion criteria

• Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form. Examples include but are not limited to uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection, active hemorrhage, and psychiatric illness.
• Patient with rapid progressive disease, warranting urgent immediate admission.
• Pregnant or breastfeeding females.
• Known HIV infection or active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI-Hepatology consultation.
• The patient has a prior or concurrent malignancy that, in the opinion of the investigator, presents a greater risk to the patient's health and survival than the MCL, with a life expectancy ≤ 1 year.
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent, or any cardiac disease defined by the New York Heart Association Classification as Class 3 (moderate) or 4 (severe).
• Prior chemotherapy within 2 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 2 weeks, radio- or toxin-immunoconjugates within 2 weeks, radiation therapy or other investigational agents within 1 week, major surgery within 4 weeks, or vaccination with live attenuated vaccines within 4 weeks of the first dose of start of assigned therapy.
• The patient receives corticosteroids for non-malignant conditions (e.g., asthma, inflammatory bowel disease) equivalent to a dexamethasone dose ≥ 4 mg/day or prednisone ≥ 20 mg/day.